HERV-K Gag RNA and Protein Levels Are Elevated in Malignant Regions of the Prostate in Males with Prostate Cancer

Viruses. 2021 Mar 10;13(3):449. doi: 10.3390/v13030449.

Abstract

Heightened expression of human endogenous retrovirus (HERV) sequences has been associated with a range of malignancies, including prostate cancer, suggesting that they may serve as useful diagnostic or prognostic cancer biomarkers. We analysed the expression of HERV-K (Gag and Env/Np9 regions), HERV-E 4.1 (Pol and Env regions), HERV-H (Pol) and HERV-W (Gag) sequences in prostate cancer cells lines and normal prostate epithelial cells using qRT-PCR. HERV expression was also analysed in matched malignant and benign prostate tissue samples from men with prostate cancer (n = 27, median age 65.2 years (range 47-70)) and compared to prostate cancer-free male controls (n = 11). Prostate cancer epithelial cell lines exhibited a signature of HERV RNA overexpression, with all HERVs analysed, except HERV-E Pol, showing heightened expression in at least two, but more commonly all, cell lines analysed. Analysis of primary prostate material indicated increased expression of HERV-E Pol but decreased expression of HERV-E Env in both malignant and benign regions of the prostate in men with prostate cancer as compared to those without. Expression of HERV-K Gag was significantly higher in malignant regions of the prostate in men with prostate cancer as compared to matched benign regions and prostate cancer-free men (p < 0.001 for both), with 85.2% of prostate cancers donors showing malignancy-associated upregulation of HERV-K Gag RNA. HERV-K Gag protein was detected in 12/18 (66.7%) malignant tissues using immunohistochemistry, but only 1/18 (5.6%) benign tissue sections. Heightened expression of HERV-K Gag RNA and protein appears to be a sensitive and specific biomarker of prostate malignancy in this cohort of men with prostate carcinoma, supporting its potential utility as a non-invasive, adjunct clinical biomarker.

Keywords: HERV-K; human endogenous retrovirus (HERV); prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Cell Line, Tumor
  • Endogenous Retroviruses / genetics*
  • Endogenous Retroviruses / isolation & purification
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Products, env / genetics*
  • Gene Products, env / metabolism
  • Gene Products, gag / genetics*
  • Gene Products, gag / metabolism
  • Gene Products, pol / genetics*
  • Gene Products, pol / metabolism
  • Humans
  • Male
  • Middle Aged
  • Prostate / metabolism
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / genetics*

Substances

  • Biomarkers, Tumor
  • Gene Products, env
  • Gene Products, gag
  • Gene Products, pol
  • Np9 protein, HERV-K, human